Variant chr17-42570011-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198204.2(MLX):c.506A>G(p.Gln169Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,613,608 control chromosomes in the GnomAD database, including 68,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5194 hom., cov: 31)

Exomes 𝑓: 0.29 ( 63274 hom. )

Consequence

MLX
NM_198204.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.51

Variant links:

Genes affected

MLX (HGNC:11645): (MAX dimerization protein MLX) The product of this gene belongs to the family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors. These factors form heterodimers with Mad proteins and play a role in proliferation, determination and differentiation. This gene product may act to diversify Mad family function by its restricted association with a subset of the Mad family of transcriptional repressors, namely, Mad1 and Mad4. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MLX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043935776).

BP6

Variant 17-42570011-A-G is Benign according to our data. Variant chr17-42570011-A-G is described in ClinVar as [Benign]. Clinvar id is 1283516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLX	NM_198204.2 link	c.506A>G	p.Gln169Arg	missense_variant	7/8	ENST00000435881.7	NP_937847.1	Q9UH92-3
MLX	NM_170607.3 link	c.668A>G	p.Gln223Arg	missense_variant	7/8		NP_733752.1	Q9UH92-1
MLX	NM_198205.2 link	c.416A>G	p.Gln139Arg	missense_variant	6/7		NP_937848.1	Q9UH92-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLX	ENST00000435881.7 link	c.506A>G	p.Gln169Arg	missense_variant	7/8	1	NM_198204.2	ENSP00000416627.1		Q9UH92-3

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38430

AN:

151920

Hom.:

5187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.284

AC:

71353

AN:

251420

Hom.:

11126

AF XY:

0.296

AC XY:

40204

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.425

Gnomad SAS exome

AF:

0.459

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.272

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.288

AC:

421119

AN:

1461570

Hom.:

63274

Cov.:

AF XY:

0.293

AC XY:

212960

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.442

Gnomad4 SAS exome

AF:

0.453

Gnomad4 FIN exome

AF:

0.247

Gnomad4 NFE exome

AF:

0.281

Gnomad4 OTH exome

AF:

0.285

GnomAD4 genome

AF:

0.253

AC:

38452

AN:

152038

Hom.:

5194

Cov.:

AF XY:

0.255

AC XY:

18919

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.416

Gnomad4 SAS

AF:

0.478

Gnomad4 FIN

AF:

0.235

Gnomad4 NFE

AF:

0.269

Gnomad4 OTH

AF:

0.271

Alfa

AF:

0.254

Hom.:

8207

Bravo

AF:

0.244

TwinsUK

AF:

0.279

AC:

1034

ALSPAC

AF:

0.293

AC:

1131

ESP6500AA

AF:

0.199

AC:

877

ESP6500EA

AF:

0.273

AC:

2350

ExAC

AF:

0.290

AC:

35245

Asia WGS

AF:

0.476

AC:

1655

AN:

3478

EpiCase

AF:

0.267

EpiControl

AF:

0.267

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2018	This variant is associated with the following publications: (PMID: 29632382, 23830516) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

.;T;.;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

T;T;T;T

MetaRNN

Benign

0.0044

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;M;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.4

N;N;N;.

REVEL

Uncertain

0.36

Sift

Benign

0.29

T;T;T;.

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.011

B;B;D;.

Vest4

0.14

MPC

0.33

ClinPred

0.067

GERP RS

4.7

Varity_R

0.37

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over